Ketogenic Diet-Based Therapy for Fatigue in Patients with Multiple Sclerosis

Background/Objectives: Fatigue is a frequent, disabling and difficult-to-treat symptom of multiple sclerosis (MS). Low-grade inflammation and energetic dysfunction have been proposed as mechanisms underlying the pathogenesis of this symptom. Owing to its anti-inflammatory and metabolic properties, there is a rationale for ketogenic diet (KD) application in this setting. The aim of this study was to evaluate the effects of KD on fatigue and other frequently associated symptoms in a carefully selected group of patients with MS. Methods: We conducted a single-arm open-label interventional study on a strictly selected group of 16 non-obese patients with multiple sclerosis who were prescribed KD for three months. Fatigue, sleep quality, daytime somnolence, mood, and quality of life were assessed at baseline (T0), 1 month (T1), and 3 months (T3) using validated scales. Results: With respect to baseline, at 3 months we observed a significant reduction in Fatigue Severity Scale (5.18 ± 1.02 vs. 4.16 ± 0.98; p = 0.042), Epworth Sleepiness Scale (8.46 ± 3.05 vs. 5.64 ± 2.46; p < 0.001), Pittsburgh Sleep Quality Index (5.64 ± 3.53 vs. 7.62 ± 2.59; p = 0.009), Depression Anxiety Stress Scales-21 depression (3.18 ± 2.93 vs. 6.15 ± 3.81; p = 0.036) and anxiety (5.15 ± 4.10 vs. 1.55 ± 1.92; p = 0.019) sub-scales, and an improvement in energy sub-scale of multiple sclerosis Quality of Life-54 (52.49 ± 12.83 vs. 37.43 ± 14.26; p = 0.042). Conclusions: These findings suggest that KD might be useful for the treatment of fatigue, and they raise interest in the use of KD in the treatment of other symptoms frequently encountered in multiple sclerosis. Larger randomized controlled studies are needed to confirm these preliminary results.